Integrin_b_cyt

SMART accession number:

SM01241

Description:

Integrins are a group of transmembrane proteins which function as extracellular matrix receptors and in cell adhesion. Integrins are ubiquitously expressed and are heterodimeric, each composed of an alpha and beta subunit. Several variations of the the alpha and beta subunits exist, and association of different alpha and beta subunits can have different a different binding specificity. This domain corresponds to the cytoplasmic domain of the beta subunit.

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [(PUBMED:12297042), (PUBMED:12361595)]. An integrin receptor is a heterodimer composed of alpha and beta subunits. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.

Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [(PUBMED:12234368)]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans [(PUBMED:14689578)]. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule [(PUBMED:2467745)]. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.

A structural mechanism of integrin alpha(IIb)beta(3) "inside-out" activation asregulated by its cytoplasmic face.

Cell. 2002; 110: 587-97

Display abstract

Activation of the ligand binding function of integrin heterodimers requirestransmission of an "inside-out" signal from their small intracellular segments totheir large extracellular domains. The structure of the cytoplasmic domain of aprototypic integrin alpha(IIb)beta(3) has been solved by NMR and reveals multiplehydrophobic and electrostatic contacts within the membrane-proximal helices ofits alpha and the beta cytoplasmic tails. The interface interactions aredisrupted by point mutations or the cytoskeletal protein talin that are known to activate the receptor. These results provide a structural mechanism by which ahandshake between the alpha and the beta cytoplasmic tails restrains the integrinin a resting state and unclasping of this interaction triggers the inside-outconformational signal that leads to receptor activation.